Preparation of vitamin



Patented Dec; 26, 1939 UNITED STATE This invention relates toimprovements in preparation of vitamin B1 and its analogous substances.

chlorine.

raemasrron or vmlmm n3 AND rrs ANALOGOUS suss'rmoas Taizo Matukawa,Kyoto, and. Masaki outs, Osaka, Japan, assignors to Kabnshiki-KaishaTakeda Ohobel Shown, Higaehi-ku, Osaka,

Japan No Drawing. Application flctober 24, ms, 8e-

rlalNo. 236,782. In Japan November 1, 193'! 1 Claim. (01. 200-251) ner Idine (VI).

following equations:

NB CN e The present invention consists bf condensing H2-methyl-4-amlno-5-thioform or form-aminomethyl-pyrimidine (V) and'm-diaceto-w-mer- (I) capto-propylalcohol (X!) by heating, with-asolvent in the presence of hydrochloric acid.

A mixture of 6 ms. -y .'y-diaceto- -'y-mercapto- Example propylalcohol,5 gms. 2-methyl-4-amino-5-iormaminomethyl-pyrimidine, and 5 c. c.glacial acetic acid containing hydrochloric acidis heated on a metalbath at 100-110 C. for 2 hours.

The product is then extracted with ether to remove ether-solublesubstances and the residueis dissolved in 100 c. c. absolute alcohol. towhich a small amount of hydrochloric acid is added. Y

The-alcoholic solution separates out crystals of vitamin 31 when it isheated for a short time or when set aside for about 12 hours. Thecrystals are filtered and purified by recrystallisation from- 0 alcohol.Yield 15' 4 grams and the melting point of the product is 245 0.

following manner:

The starting material, 2-methyl-4-amino-5- formaminomethyl-pyrimidine(V) employed in the example, is prepared in the following man Y 2-methyl4-amino-5-cyan-pyrimidine (III) is formed by the reaction ofaminomethylen malonitrile (I) with acetimid-ether (11). Using a cathodeplate coated with platinum or palladium black the product iselectrolytically reduced in an acid solution, whereby2-=methyl-4-amino-5- aminomethyl-pyrimidine (IV) is obtained. Thiscompound is reacted with formic acid to obtain2-methyl-4-amino'5-iormaminomethyl pyrimi- These chemical reactions areillustrated by the The ,other 1 starting material, (ymercapto-propylalcohol' (X1) is prepared in the'y-Aceto-y-chlor-propylalcohol (VI with an acetylating agent such asacetic anhy- ,7-diacetois treated The chemical reactionis represented bythe foldride or acetylchloride, and: the product is sublowing equation:1 jected to fractional distillation. yn-Diaceto-y- CH: n N=c--NH, -oN=c-Nm.nc1 c-* calc ,-omi -m.con+o=c---e-sn+nci cur- -cm-N n 'm m-cmon,rl-trn a 0:3

.m cm

m cm-cmoa' chlor-propylalcohoi is distilled at '12--74 C. under apressure of 2 mm. mercury.

As an alternative method, 1 mol aceto-acetic ester, 2 mols sodiumalcoholate and 1 mol ethylene chlorhydrin are reacted to producea-acetobutylolactone (VII), which in turn is treated with an acetylatingagent to obtain a,-diaceto-butylolactone (VIII). A carboxyl-group of theproduct is removed by a known process so as to produce7,7-dlflC8tO-DIOPYI81001101 (IX), which is then chlorinated to obtain'wr-diaceto-ey-chlorpropylalcoho] (X).

The final product (X1) is obtained by treating this product withpotassium hydrosulphide.

What we claim is:

processfor preparing vitamin B1 which comprises reacting2-methyl-4-amino-S-formaminomethyl-pyrimidine with7,7-di808tO-7-I118IC8Dt0- propylalcohol and glacial acetic acidcontaining hydrochloric acid.

TAIZO MATUKAWA. MASAKI OHTA.

